rs3740397

Variant names:

• chr10-102832918-G-C
• rs3740397
• NM_000102.4:c.969+75C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-102832918-G-C
• chr10-102832918-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000102.4(CYP17A1):​c.969+75C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,579,130 control chromosomes in the GnomAD database, including 112,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9971 hom., cov: 31)
  • Exomes 𝑓: 0.38 (102147 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.260
• Publications: 28 publications found

Genes affected

CYP17A1 (HGNC:2593): (cytochrome P450 family 17 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [provided by RefSeq, Jul 2008]

WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYP17A1-AS1 (HGNC:31671): (CYP17A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-102832918-G-C is Benign according to our data. Variant chr10-102832918-G-C is described in ClinVar as Benign. ClinVar VariationId is 1251511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.969+75C>G		intron_variant	Intron 5 of 7	ENST00000369887.4	NP_000093.1
CYP17A1-AS1	XR_428804.2	n.196+47G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.969+75C>G		intron_variant	Intron 5 of 7	1	NM_000102.4	ENSP00000358903.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53926 AN: 151738 Hom.: 9960 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.377 AC: 537630 AN: 1427274 Hom.: 102147 Cov.: 34 AF XY: 0.377 AC XY: 266098 AN XY: 706764

African (AFR) AF: 0.250 AC: 8152 AN: 32584

American (AMR) AF: 0.397 AC: 15784 AN: 39714

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 9395 AN: 24898

East Asian (EAS) AF: 0.428 AC: 16442 AN: 38384

South Asian (SAS) AF: 0.345 AC: 28405 AN: 82412

European-Finnish (FIN) AF: 0.365 AC: 18988 AN: 51958

Middle Eastern (MID) AF: 0.383 AC: 1713 AN: 4476

European-Non Finnish (NFE) AF: 0.381 AC: 416522 AN: 1093902

Other (OTH) AF: 0.377 AC: 22229 AN: 58946

GnomAD4 genome AF: 0.355 AC: 53967 AN: 151856 Hom.: 9971 Cov.: 31 AF XY: 0.353 AC XY: 26206 AN XY: 74196

African (AFR) AF: 0.260 AC: 10762 AN: 41414

American (AMR) AF: 0.381 AC: 5823 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1351 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2525 AN: 5126

South Asian (SAS) AF: 0.329 AC: 1581 AN: 4804

European-Finnish (FIN) AF: 0.356 AC: 3754 AN: 10536

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27116 AN: 67946

Other (OTH) AF: 0.367 AC: 769 AN: 2098

Alfa AF: 0.269 Hom.: 712

Bravo AF: 0.355

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3740397; hg19: chr10-104592675;